Plasmacytoid variant urothelial bladder cancer: Is it time to update the treatment paradigm?

ObjectivesPlasmacytoid variant (PCV) urothelial cancer (UC) of the bladder is rare, with poor clinical outcomes. We sought to identify factors that may better inform expectations of tumor behavior and improve management options in patients with PCV UC.Materials and methodsA retrospective analysis of the Indiana University Bladder Cancer Database between January 2008 and June 2013 was performed comparing 30 patients with PCV UC at cystectomy to 278 patients with nonvariant (NV) UC at cystectomy who underwent surgery for muscle-invasive disease. Multivariable logistic regression was used to assess precystectomy variables associated with non–organ-confined disease at cystectomy and Cox regression analysis to assess variables associated with mortality.ResultsPatients with PCV UC who were diagnosed with a higher stage at cystectomy (73% pT3-4 vs. 40%, P = 0.001) were more likely to have lymph node involvement (70% vs. 25%, P<0.001), and positive surgical margins were found in 40% of patients with PCV UC vs. 10% of patients with NV UC (P<0.001). Median overall survival and disease-specific survival were 19 and 22 months for PCV, respectively. Median overall survival and disease-specific survival had not been reached for NV at 68 months (P<0.001). Presence of PCV UC on transurethral resection of bladder tumor was associated with non–organ-confined disease (odds ratio = 4.02; 95% CI: 1.06–15.22; P = 0.040), and PCV at cystectomy was associated with increased adjusted risk of mortality (hazard ratio = 2.1; 95% CI: 1.2–3.8; P = 0.016).ConclusionsPCV is an aggressive UC variant, predicting non–organ-confined disease and poor survival. Differentiating between non–muscle- and muscle-invasive disease in patients with PCV UC seems less important than the aggressive nature of this disease. Instead, any evidence of PCV on transurethral resection of bladder tumor may warrant aggressive therapy.     

Muscle activity,cross-sectional area,and density following passive standing and whole body vibration: A case series

Objective

To investigate the effects of intermittent passive standing (PS) and whole body vibration (WBV) on the electromyography (EMG) activity, cross-sectional area, and density of lower extremity muscles in individuals with chronic motor complete spinal cord injury (SCI).

Design

Case series.

Methods

Seven adult men with chronic (≥2 years), thoracic motor complete (AIS A–B) SCI completed a 40-week course of thrice-weekly intermittent PS-WBV therapy, in a flexed knee posture (160°), for 45 minutes per session at a frequency of 45 Hz and 0.6–0.7 mm displacement using the WAVE^® Pro Plate, with an integrated EasyStand™ standing frame. EMG was measured in major lower extremity muscles to represent muscle activity during PS-WBV. The cross-sectional area and density of the calf muscles were measured using peripheral quantitative computed tomography at the widest calf cross-section (66% of the tibia length) at pre- and post-intervention. All measured variables were compared between the pre- and post-intervention measurements to assess change after the PS-WBV intervention.

Results

PS-WBV acutely induced EMG activity in lower extremity muscles of SCI subjects. No significant changes in lower extremity EMG activity, muscle cross-sectional area, or density were observed following the 40-week intervention.

Conclusions

Although acute exposure to PS-WBV can induce electrophysiological activity of lower extremity muscles during PS in men with motor complete SCI, the PS-WBV intervention for 40 weeks was not sufficient to result in enhanced muscle activity, or to increase calf muscle cross-sectional area or density.     

Decision-making impairment predicts 3-month hair-indexed cocaine relapse

Rationale

One of the key outstanding challenges in cocaine dependence research is determining who is at risk of relapsing during treatment.

Objectives

We examined whether cognitive decision-making profiles predict objectively (hair) indexed cocaine relapse at 3-month follow-up.

Methods

Thirty-three cocaine-dependent patients commencing outpatient treatment in a public clinic performed baseline decision-making assessments with the original and variant versions of the Iowa Gambling Task, and provided a 3-cm hair sample 3 months afterwards. Based on Iowa Gambling Tasks’ performance cut-offs, 5 patients had intact decision-making skills, 17 patients showed impaired sensitivity to reward or punishment (impairment in one of the tasks), and 9 patients showed insensitivity to future consequences (impairment in both tasks). Based on a 0.3 ng/mg cocaine cut-off, 23 patients were classified as relapsers and 10 as non-relapsers at the 3-month follow-up.

Results

Eighty percent of patients with intact decision-making were abstinent at follow-up, whereas 90 % of patients with insensitivity to future consequences had relapsed. The two subgroups (relapsers and non-relapsers) showed no significant differences on drug use, comorbidities, or psychosocial function, and significantly differed on verbal but not performance IQ. A regression model including decision-making scores and verbal IQ predicted abstinence status with high sensitivity (95 %) and moderately high specificity (81 %).

Conclusion

These preliminary findings demonstrate that decision-making profiles are associated with cocaine relapse. Moreover, combined decision-making and IQ assessments provide optimal predictive values over stimulant relapse, yielding significant opportunities for clinical translation.     

l-Leucine Supplementation Worsens the Adiposity of Already Obese Rats by Promoting a Hypothalamic Pattern of Gene Expression that Favors Fat Accumulation

Several studies showed that l-leucine supplementation reduces adiposity when provided before the onset of obesity. We studied rats that were exposed to a high-fat diet (HFD) for 10 weeks before they started to receive l-leucine supplementation. Fat mass was increased in l-leucine-supplemented rats consuming the HFD. Accordingly, l-leucine produced a hypothalamic pattern of gene expression that favors fat accumulation. In conclusion, l-leucine supplementation worsened the adiposity of rats previously exposed to HFD possibly by central mechanisms.     

Homocysteine and nitrite levels are modulated by MTHFR 677C>T polymorphism in obese women treated with simvastatin

Higher homocysteine (Hcy) levels are associated with cardiovascular risk. The aim of the present study was to evaluate the effect of simvastatin treatment on circulating Hcy levels in obese women without hypertension, diabetes or dyslipidaemia; and to determine whether the 677C>T polymorphism located in methylenetetrahydrofolate reductase (NAD(P)H) (MTHFR) gene modulates the effects of this treatment on Hcy and nitrite (as a biomarker of nitric oxide (NO) bioavailability). Twenty‐five obese women (body mass index ≥ 30 kg/m²) who had received 20 mg/day simvastatin for 6 weeks were enrolled in the study. Venous blood samples were collected to measure plasma biomarkers and gene polymorphisms. Simvastatin treatment significantly reduced total cholesterol, low‐density lipoprotein–cholesterol, thiobarbituric acid‐reactive substances, high‐sensitivity C‐reactive protein and Hcy, whereas nitrite levels were increased. The reduction in Hcy levels in carriers of the T allele was ?20.3% compared with –9.4% in patients with the CC genotype. Importantly, before treatment, nitrite levels were significantly higher in patients with the CC genotype compared with T allele carriers, whereas after treatment these levels were similar between groups. Our findings demonstrate that obese women without comorbidities and carrying the T variant of the 677C>T polymorphism of MTHFR exhibit benefits with simvastatin treatment, mainly in terms of increased NO levels.     

Statistical Evaluation of the Material-Source Effects on the DSR Rheological Properties of Plant-Mix Extracted Asphalt-Binders

The work presented in this paper was carried out to statistically evaluate and quantify the material-source effect on the asphalt-binder’s rheological properties using Analysis of Variance (ANOVA) and Tukey’s Honestly Significant Difference (Tukey´s HSD) test. The study focused on the Asphalt-Binders’ high-temperature rheological properties, namely, the G*, δ, G*/Sin(δ) and G*/(1 − (1/Tan(δ)Sin(δ))) parameters, measured using the Dynamic Shear Rheometer (DSR) device. The DSR data analyzed in the study were extracted from the Texas flexible pavements and overlays database, namely, the Texas Data Storage System (DSS), covering two Asphalt-Binders (ABs), performance grade (PG) 64-22 and PG 76-22 plant-mix extracted ABs that were treated as rolling thin film oven (RTFO) residue, and sourced from 14 different suppliers. The study findings substantiate that material-source has an effect on the high-temperature rheological properties of ABs. Additionally, it was also concluded that in as much as performance superiority and costs are crucial issues in deciding the AB source/provider, consistency and quality aspects cannot be disregarded. Therefore, material-source effects should be inclusively evaluated from both performance (rheological properties) and quality (consistence) standpoints as well as cost considerations when choosing a supplier. In general, the study contributes to the state-of-the-art enrichment on aspects of material-source effects on RTFO residue ABs’ high-temperature rheological properties, consistency, variability, and data quality.     

Corrosion of Steel Rebars in Anoxic Environments. Part I: Electrochemical Measurements

The number of reinforced concrete structures subject to anoxic conditions such as offshore platforms and geological storage facilities is growing steadily. This study explored the behaviour of embedded steel reinforcement corrosion under anoxic conditions in the presence of different chloride concentrations. Corrosion rate values were obtained by three electrochemical techniques: Linear polarization resistance, electrochemical impedance spectroscopy, and chronopotenciometry. The corrosion rate ceiling observed was 0.98 µA/cm², irrespective of the chloride content in the concrete. By means of an Evans diagram, it was possible to estimate the value of the cathodic Tafel constant (b_c) to be 180 mV dec⁻¹, and the current limit yielded an i_lim value of 0.98 µA/cm². On the other hand, the corrosion potential would lie most likely in the −900 mV_Ag/AgCl to −1000 mV_Ag/AgCl range, whilst the bounds for the most probable corrosion rate were 0.61 µA/cm² to 0.22 µA/cm². The experiments conducted revealed clear evidence of corrosion-induced pitting that will be assessed in subsequent research.     

Viruses in Extreme Environments,Current Overview,and Biotechnological Potential

Virus research has advanced significantly since the discovery of the tobacco mosaic virus (TMV), the characterization of its infection mechanisms and the factors that determine their pathogenicity. However, most viral research has focused on pathogenic viruses to humans, animals and plants, which represent only a small fraction in the virosphere. As a result, the role of most viral genes, and the mechanisms of coevolution between mutualistic viruses, their host and their environment, beyond pathogenicity, remain poorly understood. This review focuses on general aspects of viruses that interact with extremophile organisms, characteristics and examples of mechanisms of adaptation. Finally, this review provides an overview on how knowledge of extremophile viruses sheds light on the application of new tools of relevant use in modern molecular biology, discussing their value in a biotechnological context.